Osteosarcoma is the most common primary malignancy of bones and frequently affects young children and adolescents. There are several challenges associated with treating osteosarcoma owing to the ...aggressiveness of the disease, as well as the risk of chemoresistance. Numerous studies are being performed with the aim of identifying improvedprognostic and therapeutic markers for this malignancy. Maternal embryonic leucine zipper kinase (MELK) is an oncogene that has been studied in several types of cancer in recent years. In the present study, the expression of MELK in osteosarcoma and normal tissue samples was examined, and the effects of MELK expression on osteosarcoma cellular proliferation, metastasis, the cell cycle and apoptosis were demonstrated using CCK-8, wound healing, migration and invasion and apoptosis assays. The role of MELK in cancer progression in osteosarcoma was determined, revealing the association between MELK expression and prognosis of osteosarcoma. It was demonstrated that knockdown of MELK resulted in reduced proliferation, migration and invasion in vitro along with potentiation of apoptosis and cell cycle arrest. Furthermore, the effect of the targeted MELK inhibitor, OTSSP167, on tumor progression of osteosarcoma in vitro and in vivo was assessed. Mechanistically, it was demonstrated thatMELK promoted osteosarcoma proliferation and metastasis by regulating PCNA and MMP9 expression via the PI3K/Akt/mTOR signaling pathway. Thus, the present study revealed the oncogenic role played by MELK, and established MELK as a valuable prognostic and therapeutic marker in osteosarcoma.
One of the important approaches for disease control in sugarcane is to develop a disease‐resistant variety; this may be accomplished through identification of resistance genes in sugarcane. In this ...study, PCR primers targeting the conserved motifs of the nucleotide‐binding site (NBS) class and kinase class of the resistance gene analogues (RGAs) were used to amplify the RGAs from a red rot‐resistant sugarcane cultivar (Saccharum spp. hybrid) HSF 240. Upon subcloning and sequencing, fifteen putative RGAs were identified. These RGAs shared 63–98% identity to the reported disease‐resistant genes in the NCBI GenBank database. Deduced amino acid sequences also showed the presence of expected conserved domains characteristic of RGAs. Phylogenetic analysis indicated that these RGAs clustered with R genes from other plant species. The findings will be useful for studying disease‐resistant genes in sugarcane.
β-Catenin/Tcf and NF-κB pathways play an important role in biological functions. We determined the underlying mechanisms of differential interaction between two pathways in various human cancer cell ...lines. NF-κB positively regulated β-catenin/Tcf pathways in human glioblastoma, whereas it has an opposite effect on β-catenin/Tcf pathways in colon, liver, and breast cancer cells. Expression of lucine zipper tumor suppressor 2 (lzts2) was positively regulated by NF-κB activity in colon, liver, and breast cancer cells, whereas negatively regulated in glioma cells. Downregulation of lzts2 increased the β-catenin/Tcf promoter activity and inhibited NF-κB-induced modulation of the nuclear translocation of β-catenin. These data indicate that the differential crosstalk between β-catenin/Tcf and NF-κB pathway in various cancer cells is resulted from the differences in the regulation of NF-κB-induced lzts2 expression.
MD simulation study of several peptides including a polyalanine, a helix (pdb:2I9M), and a leucine zipper were carried out to investigate hydrogen bond energetics using dynamic polarized ...protein-specific charge (DPPC) to account for the polarization effect in protein dynamics. Results show that the backbone hydrogen-bond strength is generally correlated with its specific local electrostatic environment, measured by the number of water molecules near the hydrogen bond in the first solvation shell. The correlation coefficient is found to be 0.89, 0.78, and 0.80, respectively, for polyalanine, 2I9M protein, and leucine zipper. In the polyalanine, the energies of the backbone hydrogen bonds are very similar to each other due to their similar local electrostatic environment. The current study helps demonstrate and support the understanding that hydrogen bonds are stronger in a hydrophobic surrounding than in a hydrophilic one. For comparison, the result from simulation using standard force field shows a much weaker correlation between hydrogen bond energy and local electrostatic environment due to the lack of polarization effect in the force field.
Opschriften en tekstuele elementen: DUCHESSE / DE MONTAUSIER. Opschriften en tekstuele elementen: Mignard pinxit. Opschriften en tekstuele elementen: Bonvoisin sculp.t.
Inscriptions and textual ...elements: DUCHESSE / DE MONTAUSIER. Inscriptions and textual elements: Mignard pinxit. Inscriptions and textual elements: Bonvoisin sculp.t.
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